PROJECT SUMMARY Despite substantial global decline in childhood mortality rates, equivalent progress in neonatal mortality reduction has not been achieved. Severe bacterial infection affects 6.9 million neonates and causes an estimated 750 000 deaths in low-middle income countries (LMIC) annually, substantially exceeding other infectious disease-related deaths. New approaches to sepsis prevention for hospitalized and preterm newborns in LMIC are urgently needed as antimicrobial resistance threatens the few remaining therapeutic options. The paucity of data on neonatal sepsis epidemiology is an additional obstacle to development of infection prevention interventions for low-resource settings. Care bundles are evidence-based strategies targeting healthcare-associated infections; bundles are widely- adopted and effective in high-income countries, especially in adult intensive care populations. A care bundled approach for neonatal sepsis prevention in LMIC has great potential; it is likely to be cost-effective, culturally-acceptable, empowering for mothers and potentially applicable in both hospital and community- based settings. Possible bundle elements could include emollient application, chlorhexidine gluconate body washing, promotion of a clean newborn environment, safe intravenous access and improved hand hygiene among neonatal caregivers. Our research programme entails an initial surveillance phase to better characterize the epidemiology of bacterial sepsis in hospitalized South African neonates. A series of observational studies will establish the dynamics and determinants of neonatal bacterial colonization and infection. The acceptability, feasibility and compliance indicators for at least five potential elements of a ?neonatal sepsis prevention care bundle' will be determined. A final phase will measure the feasibility and acceptability of the bundle in two observational hospital cohorts of 50 infants each. The overall impact of this research will include an advanced understanding of the epidemiology of hospital-onset sepsis in South African neonates and development of a ?neonatal sepsis prevention care bundle? for low-resource settings.